Process for preparing 4-hydroxyphenylmethylcarbinol

ABSTRACT

The present invention provides a unique and novel way of producing carbinols such as 4-hydroxyphenylmethylcarbinol (HPMC). In this new process, a ketone such as 4-hydroxyacetophenone (4-HAP) is heated under suitable hydrogenation conditions of temperature and pressure in the presence of a suitable catalyst and a basic material, and for a sufficient period of time to form HPMC.

RELATED APPLICATIONS

This patent application is a continuation-in-part of Commonly assignedpatent application Ser. No. 08/529,931 filed Sep. 18, 1995, nowabandoned which is a continuation-in-part patent application of Ser. No.08/406,350 filed Mar. 17, 1995, now U.S. Pat. No. 5,498,804.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a process for the production of4-hydroxyphenylmethylcarbinol (HPMC) [sometimes referred to as1-(4-hydroxyphenyl)ethanol-( 1,4-HPE)]by the hydrogenation of4-hydroxyaeetophenone (4-HAP).

2. Description of the Prior Art

It is known in the art to produce 4-hydroxystyrene (HSM) and derivativesthereof such as poly(4-hydroxystyrene) (PHS), which have applications inthe production of adhesives, coating compositions, photoresists, and thelike. In the PHS area, there is a need to produce such material in theleast amount of process steps in order to provide efficiency. The priorart has utilized a five-step process in order to produce PHS. We havenow found that PHS can be produced in three steps or less.

The following prior art references are disclosed in accordance with theterms of 37 CFR 1.56, 1.97, and 1.93.

U.S. Pat. No. 5,087,772 (issued Feb. 11, 1992) discloses the preparationof HSM by reacting 4-acetoxystyrene (ASM) with a suitable alcohol in thepresence of a catalytic amount of a suitable base.

European Patent Application No. 0-128-984 (publication no.), filed Aug.30, 1983, discloses a process for the production of para-vinyl phenol(HSM) by dehydrogenation of para-ethyl phenol.

European Patent Application No. 0-108-624 (publication no.), filed Nov.4, 1983, discloses a process for the production of p-vinyl phenolpolymer (polyhydroxystyrene polymer - PHS) by polymerizing p-vinylphenol (HSM) in the presence of water and iron.

U.S. Pat. No. 4,032,513 (issued Jun. 28, 1977) discloses a process ofproducing PHS by cationically polymerizing HSM in the presence of anitrile, such as CH₃ CN, using a cationic polymerization initiator in ahomogeneous reaction system.

U.S. Pat. No. 5,041,614 discloses a method for the preparation of4-acetoxystyrene (ASM) from 4-acetoxyphenylmethylcarbinol. (Note FormulaI for the structural formula for ASM).

U.S. Pat. No. 5,084,533 discloses a process for the neat hydrogenationof 4-acetoxyaceto-phenone in the production of 4-acetoxystyrene (ASM).

U.S. Pat. No. 5,151,546 discloses a process for preparing4-acetoxystyrene (ASM) by heating 4-acetoxyphenylmethylcarbinol with anacid catalyst.

U.S. Pat. No. 5,245,074 discloses a process for preparing4-acetoxystyrene (ASM) through the4-acetoxyacetophenone/4-acetoxyphenylmethylcarbinol route.

U.S. Pat. No. 5,247,124 discloses a process for preparing substitutedstyrenes such as ASM by reacting a bisarylalkyl ether in the presence ofan acid catalyst.

J. Org. Chem., (1954), 19, 1205, discloses the use of copper chromitecatalysts in the hydrogenation of ketones.

Other prior art references which relate to the present invention includeU.S. Pat. Nos. 2,276,138; 3,547,858; 4,544,704; 4,678,843; 4,689,371;4,822,862; 4,857,601; 4,868,256; 4,877,843; 4,898,916; 4,912,173;4,962,147; 4,965,400; 4,880,487; 5,264,528; 5,342,727; and U.S. Pat. No.Re. 34,122.

All of the above-cited prior art and any other references mentionedherein are incorporated herein by reference in their entirety.

SUMMARY OF THE INVENTION

The present invention provides a unique and novel way of producing4-hydroxy-phenylmethylcarbinol (HPMC). In this new process,4-hydroxyacetophenone (4-HAP) is heated under suitable hydrogenationconditions of temperature and pressure in the presence of a suitablepalladium catalyst and for a sufficient period of time to form the HPMC.Subsequently, HPMC can be dehydrated and polymerized to form PHS.

DETAILED DESCRIPTION OF THE INVENTION

In the overall scheme of preparing PHS in a limited number of processsteps, it has been unexpectedly found that the intermediate product,i.e. 4-hydroxymethylcarbinol (HPMC) can be efficiently prepared byhydrogenating 4-hydroxyacetophenone (4-HAP) under certain conditions.Specifically, it has been found that 4-HAP can be heated under suitablehydrogenation conditions of temperature and pressure in the presence ofa suitable palladium catalyst and for a sufficient period of time toform HPMC in relatively high yields. The heating is conducted at atemperature of at least about 20° C., preferably from about 20° C. toabout 100° C., in the presence of at least a stoiehiometric amount ofhydrogen and a catalyst selected from the group consisting of Pd/C;Pd/Al₂ O₃ ; Pd/SiO₂ ; and Pd/CaCO₃.

In a preferred embodiment, the reaction is conducted until a substantialcompletion of hydrogenation is indicated by a lack of H₂ uptake,normally about one to twelve hours.

In a preferred embodiment, when Pd/C is used, the reaction proceeds at apressure of from about 14.7 psig to about 5,000 psig, more preferably ata pressure of from about 50 psig to about 500 psig, and most preferablyat a pressure of from about 100 psig to about 400 psig.

The hydrogenation conditions also include the use of a suitablesolvent/diluent. Diluents/solvents which can be used in the presentinvention include: (a) water; (b) hydrocarbons such as benzene, toluene,xylene, and low-boiling point petroleum fractions; (c) inorganic gasessuch as carbon monoxide, carbon dioxide, nitrogen, helium, and argon;(d) dipolar protic or aprotic solvents; and (e) mixtures thereof. Thedipolar aprotie solvents employed are solvents which have a highdielectric constant and a high dipole moment but no acid hydrogen atoms;for example, such solvents include dimethylsulfoxide (DMSO),acetonitrile, dimethylformamide (DMF), dimethylacetamide,hexamethylphosphoric acid triamide (HMPT), and n-methyl pyrrolidone(NMP). Solvents such as ethanol, methanol, or tetrahydrofuran (THF) maybe used alone or in combination with the preceding solvents/diluents.Water, ethanol, methanol, benzene, and toluene (and mixtures thereof)are preferred diluents. The diluents are used in an amount of 2 to 200mols, preferably 3 to 20 mols per mol of 4-HAP. It is to be understoodthat any diluent may be used under any temperature and reactionconditions so long as the hydrogenation of 4-HAP is effected smoothly.

The amount of catalyst employed is that which is catalytically effectivein promoting the reaction. Usually, this amount is from about 0.001weight percent to about 10.0 weight percent based on the weight of thestarting material, i.e. 4-HAP.

The length of time which this heating/hydrogenation (reaction) step isconducted is not critical and the only requirement is that the heatingbe conducted for a period sufficient to form HPMC. Generally, thisperiod is at least five minutes and may be as long as 25 hours,generally from about one to about twelve hours.

After the hydrogenation of 4-HAP, the end product (HPMC) is recoveredfrom the reaction product and the residual fraction containing anyunreacted 4-HAP can be recycled as the starting material for the nextcycle of hydrogenation. The end product (HPMC) may be recovered from thereaction product by any method. One example is to recover the HPMC as apolymerized product, i.e. the reaction product is first subjected to adecomposition and a polymerization step to polymerize the HPMC to theresulting polymer--polyhydroxystyrene (PHS).

The following specific example is supplied for the purpose of betterillustrating the invention. This example is not intended, however, tolimit or restrict the scope of the invention in any way and should notbe construed as providing conditions, parameters, or values which mustbe utilized exclusively in order to practice the present invention.

While the above has been described using 4-hydroxyacetophenone (4-HAP)as the starting material, it is also within the scope of the presentinvention to use (1) other hydroxyacetophenones (wherein the hydroxysubstituents are positioned at different locations on the phenyl ring),and (2) substituted hydroxyacetophenones wherein the remaining fourhydrogen atoms (on the phenyl ring) are selectively replaced by an Rgroup, said R being selected from the group consisting of (a) C₁ -C₈alkyl; (b) C₆ H₅ ; (c) halogen (F, Cl, Br, I); (d) hydroxy; and (e) ORwhere R is the same as defined above. These hydroxyacetophenones andsubstituted hydroxyacetophenones are all suitable starting materials foruse in the present invention process. The resultant product will be ahydroxyphenylcarbinol or substituted hydroxyphenylcarbinol ("carbinol").

In another facet of the present invention, it was also found that theutilization of a basic material in the hydrogenation step results insubstantial increases in the selectivity to the desired product, i.e.the carbinol. The basic material is selected from the group consistingof (a) alkali metal hydroxides (e.g. NaOH, KOH); (b) alkaline earthmetal hydroxides (e.g. Ca(OH)₂ ; (c) alkali metal carbonates (e.g. K₂CO₃); (d) alkali metal alkoxides (e.g. NaOCH₃ and KOC(CH₃)₃); (e) alkalimetal organic acid salts (e.g. an ionic organic base such as potassiumacetate); and (f) amines (a non-ionic organic base) such as pyridine ora tri-lower-alkylamine (e.g. tripropylamine, trimethylamine, andtriethylamine). Such basic material is present in any amount which willachieve the desired end result. Thus, an effective amount will be atleast 1 ppm (part per million), preferably from about 1 ppm to about10,000 ppm, more preferably from about 25 ppm to about 1,000 ppm. Theexact mechanism is not known, however it was surprising to find thatsuch addition of the basic material to the hydrogenation step resultedin significant increases in selectivity.

EXAMPLE I

Hydrogenation of 4-Hydroxyacetophenone

4-Hydroxyacetophenone (13.6 g, 0.1 mol) was charged in a 500 ml Zipperautoclave reactor, absolute alcohol (100 ml), and 5% Pd/C (JohnsonMatthey's 21R) (1.2 g) was added. The autoclave was first checked forleaks with 100 psig of nitrogen. The autoclave was later pressurized to300 psig with hydrogen and stirred at 35° C. for three hours. Duringthis time, 0.095 mole of hydrogen was consumed (95% of the theoreticalvalue). The reaction was vented and the contents filtered through amillipore filter yielding a colorless solution. Concentration of thissolution in vacuo gave a solid. Traces of ethanol were removed viaazeotropic distillation with toluene to afford a white solid (13.8 g).Liquid chromatographic analysis of the product showed 1,4-HPE (or HPMC)(99.0%), 4-HAP (0.2%), and 4-EP (ethylphenol) (0.8%). ¹ H NMR spectrumof the product showed it to be mainly 1,4-HPE, with traces of 4-HAP.

EXAMPLES II-XII

Using the same procedure set forth in Example I, Examples II-XII werecarried out using different reaction conditions as outlined in Table 1.The results are shown in Table 1.

                                      TABLE 1                                     __________________________________________________________________________    ANALYTICAL              REACTION CONDITIONS                                   Exam-                                                                             ex. std        RUN  4-HAP                                                                             CATALYST TYPE                                                                           SOLVENT/ H.sub.2                        ple No.                                                                           HPMC                                                                              4-HAP                                                                             HSM EP TIME (g.)                                                                              & AMOUNT  AMOUNT   ADDED                                                                              COMMENTS                  __________________________________________________________________________    II  84.79                                                                             11.08                                                                             0.00                                                                              0.57                                                                             1.6 HRS                                                                            12.0                                                                              0.6 g. 5% Pd/C                                                                          48 g.                                                                             MeOH 227  45° C., white                                                          crystals                  III 74.11                                                                             0.33                                                                              0.00                                                                              16.00                                                                            1.1 HRS                                                                            18.0                                                                              1.3 g. 5% Pd/C                                                                          42 g.                                                                             MeOH 323  55° C., white                                                          crystals                  IV  83.33                                                                             0.00                                                                              0.00                                                                              10.60                                                                            3.2 HRS                                                                            6.0 0.2 g. 5% Pd/C                                                                          54 g.                                                                             MeOH 108  35° C., white                                                          crystals                  V   35.97                                                                             48.96                                                                             5.97                                                                              2.46                                                                             2.0 HRS                                                                            6.9 0.6 g. 5% Pd/C                                                                          51 g.                                                                             EtOH 270  35° C., RXN                                                            PSI 300,                                                                      white crystal             VI  47.30                                                                             41.48                                                                             5.22                                                                              2.64                                                                             1.0 HRS                                                                            6.0 0.6 g. 5% Pd/C                                                                          51 g.                                                                             EtOH **** 35° C., RXN                                                            PSI 300,                                                                      white crystal             VII 78.95                                                                             0.00                                                                              0.00                                                                              16.57                                                                            3.0 HRS                                                                            6.0 0.6 g. 5% Pd/C                                                                          50 g.                                                                             MeOH **** 35° C., RXN                                                            PSI 300,                                                                      white crystal             VIII               2.5 HRS                                                                            6.0 0.6 g. 5% Pd/C                                                                          45.5 g.                                                                           MeOH/                                                                              740  81° C., RXN                                                            PSI 300,                                                        5.6 g.                                                                            H.sub.2 O liquid after rotovap      IX  86.90                                                                             0.00                                                                              *** 10.11                                                                            2.0 HRS                                                                            8.0 0.4 g. 5% Pd/C                                                                          53.4 g.                                                                           MeOH 780  35° C., RXN                                                            PSI 300,                                                                      white crystal             X   81.36                                                                             0.86                                                                              *** 3.55                                                                             2.0 HRS                                                                            8.0 0.2 g. 5% Pd/C                                                                          53.4 g.                                                                           MeOH 530  35° C., RXN                                                            PSI 300,                                                                      white crystal             XI  28.52                                                                             69.22                                                                             *** 2.26                                                                             4.0 HRS                                                                            20.0                                                                              1.0 g. 5% Pd/C                                                                          40 g.                                                                             MeOH 390  35° C., RXN                                                            PSI 300,                                                                      white crystal             XII                4.5 HRS                                                                            20.0                                                                              1.0 g. 5% Pd/C                                                                          39.9 g.                                                                           MeOH 1140 35° C., RXN                                                            PSI 300,                                                                      white                     __________________________________________________________________________                                                        crystal               

EXAMPLE XIII

Synthesis of 4-Hydroxyphenylmethylcarbinol

To a five-gallon stainless steel reactor, a solution of4-hydroxyacetophenone (2500 g, 18.4 moles) and a 25% solution of sodiummethoxide in methanol (39.1 g, 0.26 moles) in methanol (10,000 g, 312.5moles), and palladium on carbon catalyst (ESCAT 10, 125 g) were charged.The reactor is purged three times with nitrogen (100 psi). Hydrogen isthen charged to a pressure of 300 psi and the reactor is heated to 45°C. The temperature is maintained at 45° C. for three hours at a constanthydrogen pressure of 500 psi. The reactor is cooled to 30° C. and thendischarged (12,245 g). The analysis of the solution gave a conversion of97.6% and a selectivity of 96.0% (note Table 2).

EXAMPLES XIV-XXII

Example XIII was repeated nine times using the conditions set forth inTable 2. The results are shown in Table 2.

The results of these Examples XIII-XXII are compared to those ofExamples I-XII (i.e. without the use of a basic material) and it canreadily be seen that the use of a basic material surprisingly results ina significant increase (e.g. Example VI-47.30% HPMC vs. Example XV-86.4%HPMC) in selectivity of the HPMC.

                                      TABLE 2                                     __________________________________________________________________________         Temp                                                                              Pressure                                                                           %   % Catalyst                                                  Example                                                                            °C.                                                                        psig 4-HAP                                                                             vs 4-HAP                                                                            Conversion                                                                          Selectivity                                                                         Yield                                     __________________________________________________________________________    XIII 45  500  20  5     97.6  96.0  93.7                                      XIV  35  300  10  3     92.7  96.4  89.4                                      XV   55  300  30  3     99.2  86.4  85.7                                      XVI  35  700  10  7     99.6  93.8  93.4                                      XVII 45  500  20  5     99.4  88.8  88.3                                      XVIII                                                                              55  700  10  3     92.1  95.5  88.0                                      XIX  35  700  30  3     99.4  93.5  92.9                                      XX   35  300  30  7     98.2  98.0  96.2                                      XXI  55  300  10  7     99.3  93.9  93.2                                      XXII 45  500  20  5     98.4  96.9  95.3                                      __________________________________________________________________________

EXAMPLE XXIII

Hydrogenation of 4-Hydroxyacetophenone

4-Hydroxyacetophenone (13.6 g, 0.1 mol) was charged in 500 mL Zipperautoclave reactor, absolute alcohol (100 mL), the indicated amount(Table 3) of Et₃ N (triethylamine), and 5% pd/C (Johnson Matthey's 21R)(1.2 g) was added. The autoclave was first checked for leaks with 100psig of nitrogen. The autoclave was later pressurized to 300 psig withhydrogen and stirred at 35° C. for three hours. During this time, 0.095mole of hydrogen was consumed (95% of the theoretical value). Thereaction was vented and the contents filtered through a millipore filteryielding a colorless solution. Concentration of this solution undervacuum gave a solid. Traces of ethanol were removed via azeotropicdistillation with toluene to afford a white solid (13.8 g). Liquidchromatographic analysis of the product showed 97.8% conversion and99.2% selectivity to 4-HPMC. ¹ H NMR spectrum of the product showed itto be mainly 4-HPMC with traces of 4-HAP. The results are shown in Table3.

Example XXIII was repeated four times using the conditions set forth inTable 3. The results are shown in Table 3.

                                      TABLE 3                                     __________________________________________________________________________    HYDROGENATION OF 4-HYDROXY ACETOPHENONE (4-HAP) TO                            4-HYDROXYPHENYLMETHYLCARBINOL (4-HPMC)                                        Example                                                                             4-HAP            (Additive)  H.sub.2 Press.                                                                     Convrs.                                                                            Selectivity                                                                                4-HPMC              No.   (mole)                                                                            Solvent                                                                            Catalyst (g)                                                                          (mole) t,h                                                                              t,C                                                                             psig %    4-HPMC                                                                             4-EP                                                                              4-VPM                                                                             Yield               __________________________________________________________________________                                                              %                   XXIV  0.1 Ethanol                                                                            5% Pd/C.sup.a (1.0)                                                                   Et.sub.3 N (0.01)                                                                    3.3                                                                              50                                                                              100  55.2 83.5 0.0 3.6 46.1                XXV   0.1 Ethanol                                                                            5% Pd/C.sup.a (1.0)                                                                   Et.sub.3 N (0.005)                                                                   3.5                                                                              50                                                                              150  91.4 86.5 0.0 0.9 84.2                XXVI  0.1 Ethanol                                                                            5% Pd/C.sup.a (1.3)                                                                   Et.sub.3 N (0.005)                                                                   5.0                                                                              40                                                                              200  74.9 93.7 0.0 0.4 80.4                XXVII 0.1 Ethanol                                                                            5% Pd/C.sup.a (1.2)                                                                   Et.sub.3 N (0.005)                                                                   4.0                                                                              35                                                                              250  99.4 87.3 0.0 0.6 87.5                __________________________________________________________________________     .sup.a Johnson Matthey's 21R catalyst lot no. 8D4906 was used.           

Although the invention has been illustrated by the preceding examples,it is not to be construed as being limited thereby; but rather, theinvention encompasses the generic area as hereinbefore disclosed.Various modifications and embodiments can be made without departing fromthe spirit and scope thereof.

What is claimed is:
 1. A process for preparing4-hydroxyphenylmethylcarbinol which comprises the steps of(a) heating4-hydroxyacetophenone under suitable hydrogenation conditions oftemperature and pressure in the presence of a suitable palladiumcatalyst and at least about 25 ppm of a basic material and for asufficient period of time to form said carbinol.
 2. The process as setforth in claim 1 wherein in step (a) the temperature is at least about20° C.
 3. The process as set forth in claim 1 wherein in step (a) thereaction takes place in the presence of an organic solvent.
 4. Theprocess as set forth in claim 1 wherein in step (a) the reaction takesplace in the presence of water.
 5. The process as set forth in claim 1wherein in step (a) the temperature is from about 20° C. to about 100°C.
 6. A process for preparing a carbinol which comprises the step ofheating a ketone under suitable hydrogenation conditions of temperatureand pressure in the presence of a palladium catalyst and a basicmaterial, and for a sufficient period of time to form said carbinol. 7.A process for preparing a carbinol which comprises the step of heating asubstituted ketone under suitable hydrogenation conditions oftemperature and pressure in the presence of a palladium catalyst and abasic material, and for a sufficient period of time to form saidcarbinol.
 8. The process as set forth in claim 6 wherein the temperatureis less than about 100° C. and the heating step is conducted in thepresence of a polar protic solvent.
 9. The process as set forth in claim7 wherein the temperature is less than about 100° C.; the heating stepis conducted in the presence of a polar protic solvent; and the formedcarbinol is 4-hydroxyphenylmethylcarbinol.
 10. The process as set forthin claim 1 wherein such heating is conducted in the presence of acatalyst which is Pd/C.
 11. The process as set forth in claim 6 whereinsuch heating is conducted in the presence of a catalyst which is Pd/C.12. The process as set forth in claim 1 wherein the palladium catalystis selected from the group consisting of Pd/C; Pd/Al₂ O₃ ; Pd/SiO₂ ; andPd/CaCO₃.
 13. The process as set forth in claim 1 wherein the4-hydroxyacetophenone is replaced with an acetophenone selected from thegroup consisting of a hydroxyacetophenone and a substitutedhydroxyacetophenone.
 14. The process as set forth in claim 1 wherein thebasic material is selected from the group consisting of alkali metalhydroxides, alkaline earth metal hydroxides, alkali metal carbonates,alkali metal alkoxides, alkali metal organic acid salts, amines, andmixtures thereof.
 15. The process as set forth in claim 14 wherein saidbasic material is present in an amount of from about 25 ppm to about10,000 ppm.